Intrinsic Metastabilities in the Charge Configuration of a Double Quantum Dot

We report a thermally activated metastability in a GaAs double quantum dot exhibiting real-time charge switching in diamond shaped regions of the charge stability diagram. Accidental charge traps and sensor back action are excluded as the origin of the switching. We present an extension of the canonical double dot theory based on an intrinsic, thermal electron exchange process through the reservoirs, giving excellent agreement with the experiment. The electron spin is randomized by the exchange process, thus facilitating fast, gate-controlled spin initialization. At the same time, this process sets an intrinsic upper limit to the spin relaxation time.Comment: 4 pages, 5 figures (color

GaAs Quantum Dot Thermometry Using Direct Transport and Charge Sensing

We present measurements of the electron temperature using gate defined quantum dots formed in a GaAs 2D electron gas in both direct transport and charge sensing mode. Decent agreement with the refrigerator temperature was observed over a broad range of temperatures down to 10 mK. Upon cooling nuclear demagnetization stages integrated into the sample wires below 1 mK, the device electron temperature saturates, remaining close to 10 mK. The extreme sensitivity of the thermometer to its environment as well as electronic noise complicates temperature measurements but could potentially provide further insight into the device characteristics. We discuss thermal coupling mechanisms, address possible reasons for the temperature saturation and delineate the prospects of further reducing the device electron temperature.Comment: 8 pages, 3 (color) figure

Electrosynthesized molecularly imprinted polymers for protein recognition

Molecularly imprinted polymers (MIPs) for the recognition of proteins are expected to possess high affinity through the establishment of multiple interactions between the polymer matrix and the large number of functional groups of the target. However, while highly affine recognition sites need building blocks rich in complementary functionalities to their target, such units are likely to generate high levels of non-specific binding. This paradox, that nature solved by evolution for biological receptors, needs to be addressed by the implementation of new concepts in molecular imprinting of proteins. Additionally, the structural variability, large size and incompatibility with a range of monomers made the development of protein MIPs to take a slow start. While the majority of MIP preparation methods are variants of chemical polymerization, the polymerization of electroactive functional monomers emerged as a particularly advantageous approach for chemical sensing application. Electropolymerization can be performed from aqueous solutions to preserve the natural conformation of the protein templates, with high spatial resolution and electrochemical control of the polymerization process. This review compiles the latest results, identifying major trends and providing an outlook on the perspectives of electrosynthesised protein-imprinted MIPs for chemical sensing

Electrosynthesized molecularly imprinted polyscopoletin nanofilms for human serum albumin detection

Molecularly imprinted polymers (MIPs) rendered selective solely by the imprinting with protein templates lacking of distinctive properties to facilitate strong target-MIP interaction are likely to exhibit medium to low template binding affinities. While this prohibits the use of such MIPs for applications requiring the assessment of very low template concentrations, their implementation for the quantification of high-abundance proteins seems to have a clear niche in the analytical practice. We investigated this opportunity by developing a polyscopoletin-based MIP nanofilm for the electrochemical determination of elevated human serum albumin (HSA) in urine. As reference for a low abundance protein ferritin-MIPs were also prepared by the same procedure. Under optimal conditions, the imprinted sensors gave a linear response to HSA in the concentration range of 20–100 mg/dm3, and to ferritin in the range of 120–360 mg/dm3. While as expected the obtained limit of detection was not sufficient to determine endogenous ferritin in plasma, the HSA-sensor was successfully employed to analyse urine samples of patients with albuminuria. The results suggest that MIP-based sensors may be applicable for quantifying high abundance proteins in a clinical setting

Hydrogels and Their Role in Biosensing Applications

Hydrogels play an important role in the field of biomedical research and diagnostic medicine. They are emerging as a powerful tool in the context of bioanalytical assays and biosensing. In this context, this review gives an overview of different hydrogels and the role they adopt in a range of applications. Not only are hydrogels beneficial for the immobilization and embedding of biomolecules, but they are also used as responsive material, as wearable devices, or as functional material. In particular, the scientific and technical progress during the last decade is discussed. The newest hydrogel types, their synthesis, and many applications are presented. Advantages and performance improvements are described, along with their limitations

Cross talk between Wnt/β-catenin and Irf8 in leukemia progression and drug resistance

Progression and disease relapse of chronic myeloid leukemia (CML) depends on leukemia-initiating cells (LIC) that resist treatment. Using mouse genetics and a BCR-ABL model of CML, we observed cross talk between Wnt/{beta}-catenin signaling and the interferon-regulatory factor 8 (Irf8). In normal hematopoiesis, activation of {beta}-catenin results in up-regulation of Irf8, which in turn limits oncogenic {beta}-catenin functions. Self-renewal and myeloproliferation become dependent on {beta}-catenin in Irf8-deficient animals that develop a CML-like disease. Combined Irf8 deletion and constitutive {beta}-catenin activation result in progression of CML into fatal blast crisis, elevated leukemic potential of BCR-ABL-induced LICs, and Imatinib resistance. Interestingly, activated {beta}-catenin enhances a preexisting Irf8-deficient gene signature, identifying {beta}-catenin as an amplifier of progression-specific gene regulation in the shift of CML to blast crisis. Collectively, our data uncover Irf8 as a roadblock for {beta}-catenin-driven leukemia and imply both factors as targets in combinatorial therapy

MIPs and Aptamers for Recognition of Proteins in Biomimetic Sensing

Biomimetic binders and catalysts have been generated in order to substitute the biological pendants in separation techniques and bioanalysis. The two major approaches use either “evolution in the test tube” of nucleotides for the preparation of aptamers or total chemical synthesis for molecularly imprinted polymers (MIPs). The reproducible production of aptamers is a clear advantage, whilst the preparation of MIPs typically leads to a population of polymers with different binding sites. The realization of binding sites in the total bulk of the MIPs results in a higher binding capacity, however, on the expense of the accessibility and exchange rate. Furthermore, the readout of the bound analyte is easier for aptamers since the integration of signal generating labels is well established. On the other hand, the overall negative charge of the nucleotides makes aptamers prone to non-specific adsorption of positively charged constituents of the sample and the “biological” degradation of non-modified aptamers and ionic strength-dependent changes of conformation may be challenging in some application

Cytochrom c-basierter Superoxidsensor in organischen Medien

Das Superoxid-Radikal O2- ist wegen seiner toxischen Wirkung in der Medizin von grossem Interesse. Es hat sich ausserdem als geeignetes Modellsystem zur Untersuchung von Radikal-Scavengern bewährt. Der untersuchte Sensor besteht aus an einer Goldelektrode kovalent immobilisiertem Cytochrom c und kann amperometrisch zur Bestimmung der Konzentration von Superoxid-Radikalen verwendet werden. Dies ermöglicht, die antioxidative Wirkung von Substanzen nachzuweisen, welche Superoxid-Ionen abfangen und somit die Superoxid-Konzentration im Medium verringern. Die Methode ist in rein wässrigen Systemen etabliert. Dies limitiert allerdings die Anwendung auf hydrophile Substanzen. Der Sensor kann somit nicht für die Charakterisierung der Vielzahl von antioxidativ wirksamen hydrophoben Naturprodukten, wie etwa Vitaminen, und der Bestimmung der Effektivität von kosmetischen Produkten auf Creme-Basis mit verschiedenen antioxidativen Beigaben angewendet werden. Insbesondere die Bestimmung der Gesamt-Effektivität von kosmetischen Produkten mit verschiedenen antioxidativen Zusätzen ist hier von grossem Interesse. Um diese Beschränkung aufzuheben und somit die Anwendungsbreite des Sensors erheblich zu erweitern, werden in der vorliegenden Arbeit die Elektrochemie von kovalent immobilisiertem Cytochrom c und das Detektionsverhalten des Sensors in nicht rein wässrigen Lösungen, d.h. in verschiedenen organischen Lösungsmitteln sowie Gemischen dieser Lösungsmittel mit wässrigem Puffer, untersucht. Im etablierten Sensor wird das Cytochrom c mittels des Linkers Mercaptoundecansäure kovalent an einer Goldelektrode immobilisiert. Dessen Schwefel-Gruppe bindet an die Oberfläche der Goldelektrode; die Säurefunktion wird an Lysin-Reste des Cytochrom c kovalent gebunden

Shared autonomic pathways connect bone marrow and peripheral adipose tissues across the central neuraxis

Bone marrow adipose tissue (BMAT) is increased in both obesity and anorexia. This is unique relative to white adipose tissue (WAT), which is generally more attuned to metabolic demand. It suggests that there may be regulatory pathways that are common to both BMAT and WAT and also those that are specific to BMAT alone. The central nervous system (CNS) is a key mediator of adipose tissue function through sympathetic adrenergic neurons. Thus, we hypothesized that central autonomic pathways may be involved in BMAT regulation. To test this, we first quantified the innervation of BMAT by tyrosine hydroxylase (TH) positive nerves within the metaphysis and diaphysis of the tibia of B6 and C3H mice. We found that many of the TH+ axons were concentrated around central blood vessels in the bone marrow. However, there were also areas of free nerve endings which terminated in regions of BMAT adipocytes. Overall, the proportion of nerve-associated BMAT adipocytes increased from proximal to distal along the length of the tibia (from ~3-5 to ~14-24%), regardless of mouse strain. To identify the central pathways involved in BMAT innervation and compare to peripheral WAT, we then performed retrograde viral tract tracing with an attenuated pseudorabies virus (PRV) to infect efferent nerves from the tibial metaphysis (inclusive of BMAT) and inguinal WAT (iWAT) of C3H mice. PRV positive neurons were identified consistently from both injection sites in the intermediolateral horn of the spinal cord, reticular formation, rostroventral medulla, solitary tract, periaqueductal gray, locus coeruleus, subcoeruleus, Barrington\u27s nucleus, and hypothalamus. We also observed dual-PRV infected neurons within the majority of these regions. Similar tracings were observed in pons, midbrain, and hypothalamic regions from B6 femur and tibia, demonstrating that these results persist across mouse strains and between skeletal sites. Altogether, this is the first quantitative report of BMAT autonomic innervation and reveals common central neuroanatomic pathways, including putative command neurons, involved in coordinating multiple aspects of sympathetic output and facilitation of parallel processing between bone marrow/BMAT and peripheral adipose tissue